The proposed Mayo Clinic SPORE in Pancreatic Cancer will facilitate and promote research in pancreatic cancer that is highly likely to result in benefit to patients who currently have very little hope or treatment options. With a paucity of research in pancreatic cancer, our emphasis is on the discovery of novel mechanisms and pathways that will elucidate the etiology and pathogenesis of pancreatic carcinoma, which in turn can translate into strategies for prevention, early detection, and treatment. Led by senior pancreatic cancer researchers, our SPORE has a significant research and patient base. Annually, physicians at Mayo Clinic see approximately 450 patients with pancreatic cancer, which alone constitutes 1.5% of all pancreatic cancer cases in the United States. All of the proposed projects have a scientific base with a translational trajectory. Project #1 will provide one of the most definitive means to study the role of candidate genes and environment in the etiology of pancreatic adenocarcinoma. Project #2 will include both a retrospective cohort study to characterize the optimal criteria for screening diabetic patients with undiagnosed pancreatic cancer and identify markers that discriminate patients with diabetes mellitus that is apparently caused by pancreatic cancer. Project #3 will examine the mechanisms of action and role of Vavl protooncogene in pancreatic cancer. Project #4 will examine the role of the mechanism and role of the BRCA2 gene in pancreatic cancer. Project #5 will utilize transgenic animal models of pancreatic cancer to evaluate therapeutic combinations of vaccine, COX-2 inhibitors, and chemo/radiation. We will make particular efforts to encourage pilot studies that utilize the core resources to understand pancreatic cancer. Following a formal, rigorous review process, this SPORE will thus fund up to six developmental projects annually. We will support career development of junior faculty who will be expected to build independent programs in translational pancreatic cancer research. Four cores Administrative Core, Patient Registry and Biospecimens Core, Animal Models and Xenograft Core, and Biostatistics Core) will support the research projects. An External Advisory Committee and internal Scientific Advisory Committee will provide scientific input and guidance, and broad institutional support will enhance the infrastructure of this SPORE.